Antibacterials Flashcards
What is the mechanism for Tetracyclines?
Transport into cell
Mechanism
-cidal or -static?
- Transported into cells by protein-carrier system
- Prevent attachment of aminoacyl-tRNA bind to 30s ribosomal subunits.
- Is bacteriostatic
What is the most common method for Tetracycline resistance?
- Drug efflux pump - cross resistance common
What are tetracyclines “preferred” agents for?
“Unusual” bugs:
Rickettsia
Lyme disease (Borrelia)
Chlamydia, Mycoplasma, Ureaplasma
Chancroid (Haemophilus ducreyi)
What are two examples of Tetracyclines?
- Doxycycline
- Minocycline
- When would Doxycycline be used instead of Minocycline?
- When and why would Minocycline be prefered?
- What diseases is doxy and mino both an alternative treatment for?
- What is an important chemical aspect of tetracyclines?
- For patients with impaired renal function
- For prophylaxis of N. meningitidis because it is most lipophilic
- PenG-sensitive syphilis and uncomplicated gonorrhea
- Calcium binding: minocycline > doxycycline
- What route/routes is tetracycline available for administration?
- What additional instructions should be given with oral route?
- Oral and Parenteral
- Don’t take with calcium containing foods, antacids etc: due to calcium binding reducing efficacy/potency.
What are the most significant side effects for tetracyclines other than nausea/vomitting?
- Enterocolitis
- Candida superinfection in colon
- Photosensitization with rash
- Teeth discoloration: avoid in children & pregnancy
- What new drug class is Tigecycline (2006) part?
- What is the mechanism for Tigecycline?
- What is the benefit regarding resistance?
- Glycylcyclines: a glycylamido modification of minocycline
- Same as Tetracyclines (30s binding) but also binds to additional unique site in the ribosome
- No cross-resistance with other antibacterials including tetracyclines
- What are the primary uses for Tigecycline?
- What is its bacteriostatic profile?
- Skin/skin structure infections
complicated intra-abdominal
community-acquired pneumonia. -
G-: E.coli, Citrobacter, Klebsiella, Enterobacter
* *G+:** Staph (MSSA & MRSA), Strep
* *Anaerobes:** Bacteroides, C. perfringens
- What is the primary side effect of Tigecycline?
- What was the FDA alert released in 2010?
- Enterocolitis, also calcium binding
- Increased risk of death: use as last resort.
What is the mechanism of Chloramphenicol?
Interferes with aminoacyl-tRNA binding to 50s** ribosome** and inhibits peptide bond formation. It is bacteriostatic.
- What is the bacteriostatic profile of Chloramphenicol?
- What limits its use?
- Broad spectrum: aerobes and anaerobes, G+ & G-
- Severity of side effects.
What are the two most common current indications for Chloramphenicol?
- Meningitis: alternative for cephalosporin allergy
- Brain abcesses
What are the major side effects for Chloramphenicol?
- Bone marrow depression: Fatal aplastic anemia (1 : 30,000)
- Grey baby syndrome
- Optic neuritis and blindness
What are the primary examples of Macrolides for this course?
- Erythromycin
- Clarithromycin
- Azithromycin
What is the mechanism for the bacteriostatic action of Macrolides?
Binds to 50s subunit, blocks translocation along ribosomes
What is the static profile for Erythromycin?
- G+: Strep. infections in penicillin allergy, Staph.
- “Unusual” bugs: Chlamydia, Mycoplasma, Legionella, Bordetella
What are the primary side effects for Erythromycin?
- Nausea, vomiting: enhanced GI motility
- Inhibition of CYP3A metabolism
- Increased risk of arrythmia and cardiac arrest
Why would Clarithromycin be preferred over Erythromycin?
- Better kinetics: less frequent dosing
- Less GI motility effects (~50% less)
- Somewhat wider antibacterial spectrum
What are the primary indications for Clarithromycin?
- Haemophilus influenzae, Moraxella
- Pen. resistant Strep. pneumoniae
- Atypical mycobacteria
- Helicobacter pylori (clarithro + amoxicillin + acid blocker)
- What is Azythromycin most frequently used for?
- Outpatient respiratory tract infections: Pneumonia
- Genital infections: Chlamydia
- What is unique about Azithromycin that increases its utility?
- What is the order of severity of side effects among the macrolides?
- What cardiac effect can Erythromycin and Azithromycin have?
- High tissue levels even after cessation of drug: 3 day elimination
- Erythromycin > Clarithromycin > Azithromycin
- QT prolongation
- What is the mechanism for Clindamycin?
- What is its significant side effect?
- Binds to 50s ribosomal subunit, blocks translocation along ribosomes
- Enterocolitis : C. diff
Hepatotoxicit
What is the bacteriostatic profile for Clindamycin?
- G+ cocci: Strep. and MSSA, flesh-eating streptococci, not for enterococcus
- Anaerobes: including Bacteroides fragilis, not for C.Diff
- What is the class for Linezolid?
- What is its mechanism?
- What is the bacterio__static profile for Linezolid?
- Oxazilidinone
- Inhibits protein synthesis
Binds 50s ribosome subunit, interfering with formation of 70s initiation complex - Staph. and Enterococcus
What are the approved uses for Linezolid?
- VRE
- Staph. aureus (MRSA, MSSA)
- Strep. grp A and B
- Strep. pneumoniae
- Staph. pneumonia
What are the side effects for Linezolid?
- Non-selective inhibitor of MAO
- Diarrhea, superinfection including enterocolitis
- Headache, Nausea/vomiting
- Bone marrow suppression
What are the two examples of anti-folate drugs that inhibit folate synthesis?
- Sulfamethoxazole, Sulfadiazine
- Trimethoprim
What is the bacteriostatic mechanism for Sulfonamides?
Competitive analogue of p-aminobenzoic acid, a precursor in folate synthesis